@article{8284,
  abstract     = {Multiple resistance and pH adaptation (Mrp) antiporters are multi-subunit Na+ (or K+)/H+ exchangers representing an ancestor of many essential redox-driven proton pumps, such as respiratory complex I. The mechanism of coupling between ion or electron transfer and proton translocation in this large protein family is unknown. Here, we present the structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. It is a dimer of seven-subunit protomers with 50 trans-membrane helices each. Surface charge distribution within each monomer is remarkably asymmetric, revealing probable proton and sodium translocation pathways. On the basis of the structure we propose a mechanism where the coupling between sodium and proton translocation is facilitated by a series of electrostatic interactions between a cation and key charged residues. This mechanism is likely to be applicable to the entire family of redox proton pumps, where electron transfer to substrates replaces cation movements.},
  author       = {Steiner, Julia and Sazanov, Leonid A},
  issn         = {2050084X},
  journal      = {eLife},
  publisher    = {eLife Sciences Publications},
  title        = {{Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter}},
  doi          = {10.7554/eLife.59407},
  volume       = {9},
  year         = {2020},
}

@article{8285,
  abstract     = {We demonstrate the utility of optical cavity generated spin-squeezed states in free space atomic fountain clocks in ensembles of 390 000 87Rb atoms. Fluorescence imaging, correlated to an initial quantum nondemolition measurement, is used for population spectroscopy after the atoms are released from a confining lattice. For a free fall time of 4 milliseconds, we resolve a single-shot phase sensitivity of 814(61) microradians, which is 5.8(0.6) decibels (dB) below the quantum projection limit. We observe that this squeezing is preserved as the cloud expands to a roughly 200  μm radius and falls roughly 300  μm in free space. Ramsey spectroscopy with 240 000 atoms at a 3.6 ms Ramsey time results in a single-shot fractional frequency stability of 8.4(0.2)×10−12, 3.8(0.2) dB below the quantum projection limit. The sensitivity and stability are limited by the technical noise in the fluorescence detection protocol and the microwave system, respectively.},
  author       = {Malia, Benjamin K. and Martínez-Rincón, Julián and Wu, Yunfan and Hosten, Onur and Kasevich, Mark A.},
  issn         = {1079-7114},
  journal      = {Physical Review Letters},
  number       = {4},
  publisher    = {American Physical Society},
  title        = {{Free space Ramsey spectroscopy in rubidium with noise below the quantum projection limit}},
  doi          = {10.1103/PhysRevLett.125.043202},
  volume       = {125},
  year         = {2020},
}

@inproceedings{8287,
  abstract     = {Reachability analysis aims at identifying states reachable by a system within a given time horizon. This task is known to be computationally expensive for linear hybrid systems. Reachability analysis works by iteratively applying continuous and discrete post operators to compute states reachable according to continuous and discrete dynamics, respectively. In this paper, we enhance both of these operators and make sure that most of the involved computations are performed in low-dimensional state space. In particular, we improve the continuous-post operator by performing computations in high-dimensional state space only for time intervals relevant for the subsequent application of the discrete-post operator. Furthermore, the new discrete-post operator performs low-dimensional computations by leveraging the structure of the guard and assignment of a considered transition. We illustrate the potential of our approach on a number of challenging benchmarks.},
  author       = {Bogomolov, Sergiy and Forets, Marcelo and Frehse, Goran and Potomkin, Kostiantyn and Schilling, Christian},
  booktitle    = {Proceedings of the International Conference on Embedded Software},
  keywords     = {reachability, hybrid systems, decomposition},
  location     = {Virtual },
  title        = {{Reachability analysis of linear hybrid systems via block decomposition}},
  year         = {2020},
}

@misc{8294,
  abstract     = {Automated root growth analysis and tracking of root tips. },
  author       = {Hauschild, Robert},
  publisher    = {IST Austria},
  title        = {{RGtracker}},
  doi          = {10.15479/AT:ISTA:8294},
  year         = {2020},
}

@article{8308,
  abstract     = {Many-body localization provides a mechanism to avoid thermalization in isolated interacting quantum systems. The breakdown of thermalization may be complete, when all eigenstates in the many-body spectrum become localized, or partial, when the so-called many-body mobility edge separates localized and delocalized parts of the spectrum. Previously, De Roeck et al. [Phys. Rev. B 93, 014203 (2016)] suggested a possible instability of the many-body mobility edge in energy density. The local ergodic regions—so-called “bubbles”—resonantly spread throughout the system, leading to delocalization. In order to study such instability mechanism, in this work we design a model featuring many-body mobility edge in particle density: the states at small particle density are localized, while increasing the density of particles leads to delocalization. Using numerical simulations with matrix product states, we demonstrate the stability of many-body localization with respect to small bubbles in large dilute systems for experimentally relevant timescales. In addition, we demonstrate that processes where the bubble spreads are favored over processes that lead to resonant tunneling, suggesting a possible mechanism behind the observed stability of many-body mobility edge. We conclude by proposing experiments to probe particle density mobility edge in the Bose-Hubbard model.},
  author       = {Brighi, Pietro and Abanin, Dmitry A. and Serbyn, Maksym},
  issn         = {2469-9969},
  journal      = {Physical Review B},
  number       = {6},
  publisher    = {American Physical Society},
  title        = {{Stability of mobility edges in disordered interacting systems}},
  doi          = {10.1103/physrevb.102.060202},
  volume       = {102},
  year         = {2020},
}

@article{8318,
  abstract     = {Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I.},
  author       = {Gutierrez-Fernandez, Javier and Kaszuba, Karol and Minhas, Gurdeep S. and Baradaran, Rozbeh and Tambalo, Margherita and Gallagher, David T. and Sazanov, Leonid A},
  issn         = {20411723},
  journal      = {Nature Communications},
  number       = {1},
  publisher    = {Springer Nature},
  title        = {{Key role of quinone in the mechanism of respiratory complex I}},
  doi          = {10.1038/s41467-020-17957-0},
  volume       = {11},
  year         = {2020},
}

@article{8319,
  abstract     = {We demonstrate that releasing atoms into free space from an optical lattice does not deteriorate cavity-generated spin squeezing for metrological purposes. In this work, an ensemble of 500000 spin-squeezed atoms in a high-finesse optical cavity with near-uniform atom-cavity coupling is prepared, released into free space, recaptured in the cavity, and probed. Up to ∼10 dB of metrologically relevant squeezing is retrieved for 700μs free-fall times, and decaying levels of squeezing are realized for up to 3 ms free-fall times. The degradation of squeezing results from loss of atom-cavity coupling homogeneity between the initial squeezed state generation and final collective state readout. A theoretical model is developed to quantify this degradation and this model is experimentally validated.},
  author       = {Wu, Yunfan and Krishnakumar, Rajiv and Martínez-Rincón, Julián and Malia, Benjamin K. and Hosten, Onur and Kasevich, Mark A.},
  issn         = {24699934},
  journal      = {Physical Review A},
  number       = {1},
  publisher    = {American Physical Society},
  title        = {{Retrieval of cavity-generated atomic spin squeezing after free-space release}},
  doi          = {10.1103/PhysRevA.102.012224},
  volume       = {102},
  year         = {2020},
}

@article{8320,
  abstract     = {The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications.},
  author       = {Mukba, S. A. and Vlasov, Petr and Kolosov, P. M. and Shuvalova, E. Y. and Egorova, T. V. and Alkalaeva, E. Z.},
  issn         = {16083245},
  journal      = {Molecular Biology},
  number       = {4},
  pages        = {475--484},
  publisher    = {Springer Nature},
  title        = {{Expanding the genetic code: Unnatural base pairs in biological systems}},
  doi          = {10.1134/S0026893320040111},
  volume       = {54},
  year         = {2020},
}

@article{8321,
  abstract     = {The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications.},
  author       = {Mukba, S. A. and Vlasov, Petr and Kolosov, P. M. and Shuvalova, E. Y. and Egorova, T. V. and Alkalaeva, E. Z.},
  issn         = {00268984},
  journal      = {Molekuliarnaia biologiia},
  number       = {4},
  pages        = {531--541},
  publisher    = {Russian Academy of Sciences},
  title        = {{Expanding the genetic code: Unnatural base pairs in biological systems}},
  doi          = {10.31857/S0026898420040126},
  volume       = {54},
  year         = {2020},
}

@inproceedings{8322,
  abstract     = {Reverse firewalls were introduced at Eurocrypt 2015 by Miro-nov and Stephens-Davidowitz, as a method for protecting cryptographic protocols against attacks on the devices of the honest parties. In a nutshell: a reverse firewall is placed outside of a device and its goal is to “sanitize” the messages sent by it, in such a way that a malicious device cannot leak its secrets to the outside world. It is typically assumed that the cryptographic devices are attacked in a “functionality-preserving way” (i.e. informally speaking, the functionality of the protocol remains unchanged under this attacks). In their paper, Mironov and Stephens-Davidowitz construct a protocol for passively-secure two-party computations with firewalls, leaving extension of this result to stronger models as an open question.
In this paper, we address this problem by constructing a protocol for secure computation with firewalls that has two main advantages over the original protocol from Eurocrypt 2015. Firstly, it is a multiparty computation protocol (i.e. it works for an arbitrary number n of the parties, and not just for 2). Secondly, it is secure in much stronger corruption settings, namely in the active corruption model. More precisely: we consider an adversary that can fully corrupt up to 𝑛−1 parties, while the remaining parties are corrupt in a functionality-preserving way.
Our core techniques are: malleable commitments and malleable non-interactive zero-knowledge, which in particular allow us to create a novel protocol for multiparty augmented coin-tossing into the well with reverse firewalls (that is based on a protocol of Lindell from Crypto 2001).},
  author       = {Chakraborty, Suvradip and Dziembowski, Stefan and Nielsen, Jesper Buus},
  booktitle    = {Advances in Cryptology – CRYPTO 2020},
  isbn         = {9783030568795},
  issn         = {16113349},
  location     = {Santa Barbara, CA, United States},
  pages        = {732--762},
  publisher    = {Springer Nature},
  title        = {{Reverse firewalls for actively secure MPCs}},
  doi          = {10.1007/978-3-030-56880-1_26},
  volume       = {12171},
  year         = {2020},
}

@article{8323,
  author       = {Pach, János},
  issn         = {14320444},
  journal      = {Discrete and Computational Geometry},
  pages        = {571--574},
  publisher    = {Springer Nature},
  title        = {{A farewell to Ricky Pollack}},
  doi          = {10.1007/s00454-020-00237-5},
  volume       = {64},
  year         = {2020},
}

@inproceedings{8324,
  abstract     = {The notion of program sensitivity (aka Lipschitz continuity) specifies that changes in the program input result in proportional changes to the program output. For probabilistic programs the notion is naturally extended to expected sensitivity. A previous approach develops a relational program logic framework for proving expected sensitivity of probabilistic while loops, where the number of iterations is fixed and bounded. In this work, we consider probabilistic while loops where the number of iterations is not fixed, but randomized and depends on the initial input values. We present a sound approach for proving expected sensitivity of such programs. Our sound approach is martingale-based and can be automated through existing martingale-synthesis algorithms. Furthermore, our approach is compositional for sequential composition of while loops under a mild side condition. We demonstrate the effectiveness of our approach on several classical examples from Gambler's Ruin, stochastic hybrid systems and stochastic gradient descent. We also present experimental results showing that our automated approach can handle various probabilistic programs in the literature.},
  author       = {Wang, Peixin and Fu, Hongfei and Chatterjee, Krishnendu and Deng, Yuxin and Xu, Ming},
  booktitle    = {Proceedings of the ACM on Programming Languages},
  issn         = {2475-1421},
  number       = {POPL},
  publisher    = {ACM},
  title        = {{Proving expected sensitivity of probabilistic programs with randomized variable-dependent termination time}},
  doi          = {10.1145/3371093},
  volume       = {4},
  year         = {2020},
}

@article{8325,
  abstract     = {Let 𝐹:ℤ2→ℤ be the pointwise minimum of several linear functions. The theory of smoothing allows us to prove that under certain conditions there exists the pointwise minimal function among all integer-valued superharmonic functions coinciding with F “at infinity”. We develop such a theory to prove existence of so-called solitons (or strings) in a sandpile model, studied by S. Caracciolo, G. Paoletti, and A. Sportiello. Thus we made a step towards understanding the phenomena of the identity in the sandpile group for planar domains where solitons appear according to experiments. We prove that sandpile states, defined using our smoothing procedure, move changeless when we apply the wave operator (that is why we call them solitons), and can interact, forming triads and nodes. },
  author       = {Kalinin, Nikita and Shkolnikov, Mikhail},
  issn         = {14320916},
  journal      = {Communications in Mathematical Physics},
  number       = {9},
  pages        = {1649--1675},
  publisher    = {Springer Nature},
  title        = {{Sandpile solitons via smoothing of superharmonic functions}},
  doi          = {10.1007/s00220-020-03828-8},
  volume       = {378},
  year         = {2020},
}

@article{8329,
  abstract     = {We show the synthesis of a redox‐active quinone, 2‐methoxy‐1,4‐hydroquinone (MHQ), from a bio‐based feedstock and its suitability as electrolyte in aqueous redox flow batteries. We identified semiquinone intermediates at insufficiently low pH and quinoid radicals as responsible for decomposition of MHQ under electrochemical conditions. Both can be avoided and/or stabilized, respectively, using H 3 PO 4 electrolyte, allowing for reversible cycling in a redox flow battery for hundreds of cycles.},
  author       = {Schlemmer, Werner and Nothdurft, Philipp and Petzold, Alina and Frühwirt, Philipp and Schmallegger, Max and Gescheidt-Demner, Georg and Fischer, Roland and Freunberger, Stefan Alexander and Kern, Wolfgang and Spirk, Stefan},
  issn         = {1521-3773},
  journal      = {Angewandte Chemie International Edition},
  number       = {51},
  pages        = {22943--22946},
  publisher    = {Wiley},
  title        = {{2‐methoxyhydroquinone from vanillin for aqueous redox‐flow batteries}},
  doi          = {10.1002/anie.202008253},
  volume       = {59},
  year         = {2020},
}

@phdthesis{8332,
  abstract     = {Designing and verifying concurrent programs is a notoriously challenging, time consuming, and error prone task, even for experts. This is due to the sheer number of possible interleavings of a concurrent program, all of which have to be tracked and accounted for in a formal proof. Inventing an inductive invariant that captures all interleavings of a low-level implementation is theoretically possible, but practically intractable. We develop a refinement-based verification framework that provides mechanisms to simplify proof construction by decomposing the verification task into smaller subtasks.

In a first line of work, we present a foundation for refinement reasoning over structured concurrent programs. We introduce layered concurrent programs as a compact notation to represent multi-layer refinement proofs. A layered concurrent program specifies a sequence of connected concurrent programs, from most concrete to most abstract, such that common parts of different programs are written exactly once. Each program in this sequence is expressed as structured concurrent program, i.e., a program over (potentially recursive) procedures, imperative control flow, gated atomic actions, structured parallelism, and asynchronous concurrency. This is in contrast to existing refinement-based verifiers, which represent concurrent systems as flat transition relations. We present a powerful refinement proof rule that decomposes refinement checking over structured programs into modular verification conditions. Refinement checking is supported by a new form of modular, parameterized invariants, called yield invariants, and a linear permission system to enhance local reasoning.

In a second line of work, we present two new reduction-based program transformations that target asynchronous programs. These transformations reduce the number of interleavings that need to be considered, thus reducing the complexity of invariants. Synchronization simplifies the verification of asynchronous programs by introducing the fiction, for proof purposes, that asynchronous operations complete synchronously. Synchronization summarizes an asynchronous computation as immediate atomic effect. Inductive sequentialization establishes sequential reductions that captures every behavior of the original program up to reordering of coarse-grained commutative actions. A sequential reduction of a concurrent program is easy to reason about since it corresponds to a simple execution of the program in an idealized synchronous environment, where processes act in a fixed order and at the same speed.

Our approach is implemented the CIVL verifier, which has been successfully used for the verification of several complex concurrent programs. In our methodology, the overall correctness of a program is established piecemeal by focusing on the invariant required for each refinement step separately. While the programmer does the creative work of specifying the chain of programs and the inductive invariant justifying each link in the chain, the tool automatically constructs the verification conditions underlying each refinement step.},
  author       = {Kragl, Bernhard},
  issn         = {2663-337X},
  pages        = {120},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Verifying concurrent programs: Refinement, synchronization, sequentialization}},
  doi          = {10.15479/AT:ISTA:8332},
  year         = {2020},
}

@article{8336,
  abstract     = {Plant hormone cytokinins are perceived by a subfamily of sensor histidine kinases (HKs), which via a two-component phosphorelay cascade activate transcriptional responses in the nucleus. Subcellular localization of the receptors proposed the endoplasmic reticulum (ER) membrane as a principal cytokinin perception site, while study of cytokinin transport pointed to the plasma membrane (PM)-mediated cytokinin signalling. Here, by detailed monitoring of subcellular localizations of the fluorescently labelled natural cytokinin probe and the receptor ARABIDOPSIS HISTIDINE KINASE 4 (CRE1/AHK4) fused to GFP reporter, we show that pools of the ER-located cytokinin receptors can enter the secretory pathway and reach the PM in cells of the root apical meristem, and the cell plate of dividing meristematic cells. Brefeldin A (BFA) experiments revealed vesicular recycling of the receptor and its accumulation in BFA compartments. We provide a revised view on cytokinin signalling and the possibility of multiple sites of perception at PM and ER.},
  author       = {Kubiasova, Karolina and Montesinos López, Juan C and Šamajová, Olga and Nisler, Jaroslav and Mik, Václav and Semeradova, Hana and Plíhalová, Lucie and Novák, Ondřej and Marhavý, Peter and Cavallari, Nicola and Zalabák, David and Berka, Karel and Doležal, Karel and Galuszka, Petr and Šamaj, Jozef and Strnad, Miroslav and Benková, Eva and Plíhal, Ondřej and Spíchal, Lukáš},
  issn         = {20411723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Cytokinin fluoroprobe reveals multiple sites of cytokinin perception at plasma membrane and endoplasmic reticulum}},
  doi          = {10.1038/s41467-020-17949-0},
  volume       = {11},
  year         = {2020},
}

@article{8337,
  abstract     = {Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses.},
  author       = {Antoniadi, Ioanna and Novák, Ondřej and Gelová, Zuzana and Johnson, Alexander J and Plíhal, Ondřej and Simerský, Radim and Mik, Václav and Vain, Thomas and Mateo-Bonmatí, Eduardo and Karady, Michal and Pernisová, Markéta and Plačková, Lenka and Opassathian, Korawit and Hejátko, Jan and Robert, Stéphanie and Friml, Jiří and Doležal, Karel and Ljung, Karin and Turnbull, Colin},
  issn         = {20411723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Cell-surface receptors enable perception of extracellular cytokinins}},
  doi          = {10.1038/s41467-020-17700-9},
  volume       = {11},
  year         = {2020},
}

@inproceedings{8339,
  abstract     = {Discrete Gaussian distributions over lattices are central to lattice-based cryptography, and to the computational and mathematical aspects of lattices more broadly. The literature contains a wealth of useful theorems about the behavior of discrete Gaussians under convolutions and related operations. Yet despite their structural similarities, most of these theorems are formally incomparable, and their proofs tend to be monolithic and written nearly “from scratch,” making them unnecessarily hard to verify, understand, and extend.
In this work we present a modular framework for analyzing linear operations on discrete Gaussian distributions. The framework abstracts away the particulars of Gaussians, and usually reduces proofs to the choice of appropriate linear transformations and elementary linear algebra. To showcase the approach, we establish several general properties of discrete Gaussians, and show how to obtain all prior convolution theorems (along with some new ones) as straightforward corollaries. As another application, we describe a self-reduction for Learning With Errors (LWE) that uses a fixed number of samples to generate an unlimited number of additional ones (having somewhat larger error). The distinguishing features of our reduction are its simple analysis in our framework, and its exclusive use of discrete Gaussians without any loss in parameters relative to a prior mixed discrete-and-continuous approach.
As a contribution of independent interest, for subgaussian random matrices we prove a singular value concentration bound with explicitly stated constants, and we give tighter heuristics for specific distributions that are commonly used for generating lattice trapdoors. These bounds yield improvements in the concrete bit-security estimates for trapdoor lattice cryptosystems.},
  author       = {Genise, Nicholas and Micciancio, Daniele and Peikert, Chris and Walter, Michael},
  booktitle    = {23rd IACR International Conference on the Practice and Theory of Public-Key Cryptography},
  isbn         = {9783030453732},
  issn         = {16113349},
  location     = {Edinburgh, United Kingdom},
  pages        = {623--651},
  publisher    = {Springer Nature},
  title        = {{Improved discrete Gaussian and subgaussian analysis for lattice cryptography}},
  doi          = {10.1007/978-3-030-45374-9_21},
  volume       = {12110},
  year         = {2020},
}

@phdthesis{8340,
  abstract     = {Mitochondria are sites of oxidative phosphorylation in eukaryotic cells. Oxidative phosphorylation operates by a chemiosmotic mechanism made possible by redox-driven proton pumping machines which establish a proton motive force across the inner mitochondrial membrane. This electrochemical proton gradient is used to drive ATP synthesis, which powers the majority of cellular processes such as protein synthesis, locomotion and signalling. In this thesis I investigate the structures and molecular mechanisms of two inner mitochondrial proton pumping enzymes, respiratory complex I and transhydrogenase. I present the first high-resolution structure of the full transhydrogenase from any species, and a significantly improved structure of complex I. Improving the resolution from 3.3 Å available previously to up to 2.3 Å in this thesis allowed us to model bound water molecules, crucial in the proton pumping mechanism. For both enzymes, up to five cryo-EM datasets with different substrates and inhibitors bound were solved to delineate the catalytic cycle and understand the proton pumping mechanism. In transhydrogenase, the proton channel is gated by reversible detachment of the NADP(H)-binding domain which opens the proton channel to the opposite sites of the membrane. In complex I, the proton channels are gated by reversible protonation of key glutamate and lysine residues and breaking of the water wire connecting the proton pumps with the quinone reduction site. The tight coupling between the redox and the proton pumping reactions in transhydrogenase is achieved by controlling the NADP(H) exchange which can only happen when the NADP(H)-binding domain interacts with the membrane domain. In complex I, coupling is achieved by cycling of the whole complex between the closed state, in which quinone can get reduced, and the open state, in which NADH can induce quinol ejection from the binding pocket. On the basis of these results I propose detailed mechanisms for catalytic cycles of transhydrogenase and complex I that are consistent with a large amount of previous work. In both enzymes, conformational and electrostatic mechanisms contribute to the overall catalytic process. Results presented here could be used for better understanding of the human pathologies arising from deficiencies of complex I or transhydrogenase and could be used to develop novel therapies.},
  author       = {Kampjut, Domen},
  isbn         = {978-3-99078-008-4},
  issn         = {2663-337X},
  pages        = {242},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes}},
  doi          = {10.15479/AT:ISTA:8340},
  year         = {2020},
}

@phdthesis{8341,
  abstract     = {One of the most striking hallmarks of the eukaryotic cell is the presence of intracellular vesicles and organelles. Each of these membrane-enclosed compartments has a distinct composition of lipids and proteins, which is essential for accurate membrane traffic and homeostasis. Interestingly, their biochemical identities are achieved with the help
of small GTPases of the Rab family, which cycle between GDP- and GTP-bound forms on the selected membrane surface. While this activity switch is well understood for an individual protein, how Rab GTPases collectively transition between states to generate decisive signal propagation in space and time is unclear. In my PhD thesis, I present
in vitro reconstitution experiments with theoretical modeling to systematically study a minimal Rab5 activation network from bottom-up. We find that positive feedback based on known molecular interactions gives rise to bistable GTPase activity switching on system’s scale. Furthermore, we determine that collective transition near the critical
point is intrinsically stochastic and provide evidence that the inactive Rab5 abundance on the membrane can shape the network response. Finally, we demonstrate that collective switching can spread on the lipid bilayer as a traveling activation wave, representing a possible emergent activity pattern in endosomal maturation. Together, our
findings reveal new insights into the self-organization properties of signaling networks away from chemical equilibrium. Our work highlights the importance of systematic characterization of biochemical systems in well-defined physiological conditions. This way, we were able to answer long-standing open questions in the field and close the gap between regulatory processes on a molecular scale and emergent responses on system’s level.},
  author       = {Bezeljak, Urban},
  issn         = {2663-337X},
  pages        = {215},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{In vitro reconstitution of a Rab activation switch}},
  doi          = {10.15479/AT:ISTA:8341},
  year         = {2020},
}